Male Alopecia: Treatment Update

Ken Washenik MD PhD Bosley / Aderans Research Institute

New York University School of Medicine

Disclosure:• Bosley / Aderans Research

- Employee, salary, stock options, royalties

• Allergan - Advisor

• Johnson and Johnson Healthcare Products- Clinical investigator

• Merck – Speaker Bureau

• Boards of Directors- North American Hair Research Society- Cicatricial Alopecia Research Foundation- Hair Foundation

• Off-label use discussed

Dihydrotestosterone is the principal androgen causing hair loss in men, but probably not in women

Androgens and Follicle Miniaturization in Androgenetic Alopecia

Targets for Pharmacologic Therapy in Androgenetic Alopecia

• The follicular miniaturization caused by the shortening of the anagen phase- Anagen induction and prolongation

agents- Minoxidil

Increased Scalp Coverage with Minoxidil Solution

5%

minox

2%

minoxVehicle

Frontal1 51% 42% 13%

Vertex2 54% 38% 17%

Patients with at least slight increase in scalp coverage judged by photographic review at 48 weeks

1Olsen EA et al AAD 2003; Poster #397 2Olsen EA et al JAAD 2002;47:377-385

Minoxidil: Mechanism of Action

• Not related to androgens

• Direct stimulator of follicular growth (VEGF and prostaglandin synthase)1

• Anagen induction and prolongation

1Messenger and Rundegren. Br J Dermatol 2004;150:186-94

Targets for Pharmacologic Therapy in Androgenetic Alopecia

• The follicular miniaturization caused by the shortening of the anagen phase- Anagen induction and prolongation

agents- Minoxidil- Prostaglandin analogs / prostamides

Prostaglandins and Hair Growth

• Latanoprost Solution (Xalatan)

- Eye drops for glaucoma

- Prostaglandin F2analog

- 77% developed increased eyelash growth (317 patients)

- Applied once daily for 4 months (avg)

Demitsu et al JAAD 44:721-723 (2001)

Uno et al. Acta Derm Venereol 82: 7-12 (2002)

Prostaglandins and Hair Growth

Approved as a stimulator of eyelash growth in 2008

• 0.3 % bimatoprost ophthalmic solution, qD x 16 wks

Law SK. Clin Ophthalmol. 2010; 4: 349–358.

http://latisse.com/ClinicalTrialGallery.aspx?state=24

Prostaglandins and Hair Growth

• Phase I trial of topical bimatoprost in MPHL and FPHL underway

http://www.clinicaltrials.gov

Targets for Pharmacologic Therapy in Androgenetic Alopecia

• The follicular miniaturization caused by the shortening of the anagen phase

• Dihydrotestosterone (DHT)- Synthesis inhibitors

- Finasteride

Mechanism of Action of Finasteride

O

OH

Testosterone

NADPH

5-ReductaseType II

O

OH

DHT

FinasterideO NH

CONHC(CH3)3

Decreased 60 – 70%

Global Photographic Assessment

- 10% lost hair

- 48% gained hair

90% gained or did not lose hair

Increase

No Change

- 42% no loss

Vertex Data

Finasteride 1 mg for 5 years Men 18-41 years old

European Journal of Dermatology. 2002; 12: 38-49

Photographic Assessment

Finasteride 1 mg

Targets for Pharmacologic Therapy in Androgenetic Alopecia

• The follicular miniaturization caused by the shortening of the anagen phase

• Dihydrotestosterone- Synthesis inhibitors

- Finasteride- Dutasteride (not approved for AGA)

Dutasteride: A Dual 5 -Reductase Inhibitor

• Inhibits type 1 and 2 enzymes- Lowers DHT by ~90%

• FDA approved for prostate indication (BPH)

• Six month Phase II study indicated better efficacy than finasteride*

• Long 5 week half life

• Safety data consistent with DHT reductionPossibility of prolonged reduction in sperm count

added to label*Olsen et al. J Am Acad Dermatol. 2006 Dec;55(6):1014-23

Eun et al. J Am Acad Dermatol 2010;63:252-8

Eun et al. J Am Acad Dermatol 2010;63:252-8

Eun et al. J Am Acad Dermatol 2010;63:252-8

Dut (N=73) Plac (N=75)

Dutasteride Phase III Study

Eun et al. J Am Acad Dermatol 2010;63:252-8

Investigator Assessment: Slight, Moderate or Great Increase

61.6% Dutast 20.0% Placebo

Safety: Finasteride

FIN 1MG(N = 945)

1.8

1.3

Percentage of Patients :

Decreased Libido

Erectile Dysfunction

Phase III 1 Year Studies

1.3

0.7

PBO(N = 934)

Phase III 5 Year Studies (N = 323) (N = 23)

Decreased LibidoErectile Dysfunction

0.30.3

00

Controversy Over Reports of Persistent Sexual Side Effects

• Post Marketing reports of persistent sexual side effects

• Label indicating these reports in Sweden and UK

• Two recent manuscripts discussing these types of reports in the Journal of Sexual Medicine

• Class action lawsuit in CanadaJ Sex Med.1743-6109.2010 and 1743-6109.2011

Update on Medical Treatment

• Anagen prolongation agents- Bimatoprost in clinical development for MPHL

and FPHL- 5% minoxidil foam in clinical trials for FPHL

• 5 alpha reductase inhibitors- Dutasteride approved for MPHL in Korea- Controversy concerning reports of persistent

side effects

Emerging Therapies

• Follicle Regeneration- Follicle Cell Transplantation

Important Cells for Follicle Regeneration

Epidermal Cells

Dermal Cells

Inducer Responder

Isolate, Multiply and Inject Trichogenic Cells

Clinical Trial Status of Follicle Cell Transplantation

• Phase I completed in UK in 2008

• Phase II testing currently underway for male pattern hair loss (MPHL) and FPHL in the US

• Iterative series of protocols enrolling 20 – 40 subjects per protocol

• Only early interim data available

Baseline Week 12

Macrophotographic Assessment

Unpublished data: Aderans Research Institute

+33.7% Total hair count (+115)+53.8% Terminal hair count (≥ 30µm)+10.7% Vellus hair count (<30 µm)

Excision 54 Weeks

Macrophotographic Assessment

Unpublished data: Aderans Research Institute

Thank You